259 research outputs found

    Molecular aspects of tumor cell migration and invasion.

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    Cell migration and invasion are crucial steps in many physiological events. However, they are also implicated in the physiopathology of many diseases, such as cancer. To spread through the tissues, tumor cells use mechanisms that involve several molecular actors: adhesion receptor families, receptor tyrosine kinases, cytoskeleton proteins, adapter and signalling proteins interplay in a complex scenario. The balance of cellular signals for proliferation and survival responses also regulates migratory behaviours of tumor cells. To complicate the scene of crime drug resistance players can interfere thus worsening this delicate situation. The complete understanding of this molecular jungle is an impossible mission: some molecular aspects are reviewed in this paper

    Liposomes as nanomedical devices

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    Giuseppina Bozzuto,1,2 Agnese Molinari2 1Chemical Methodology Institute, CNR, 2Department of Technology and Health, Istituto Superiore di Sanità, Rome, Italy Abstract: Since their discovery in the 1960s, liposomes have been studied in depth, and they continue to constitute a field of intense research. Liposomes are valued for their biological and technological advantages, and are considered to be the most successful drug-carrier system known to date. Notable progress has been made, and several biomedical applications of liposomes are either in clinical trials, are about to be put on the market, or have already been approved for public use. In this review, we briefly analyze how the efficacy of liposomes depends on the nature of their components and their size, surface charge, and lipidic organization. Moreover, we discuss the influence of the physicochemical properties of liposomes on their interaction with cells, half-life, ability to enter tissues, and final fate in vivo. Finally, we describe some strategies developed to overcome limitations of the “first-generation” liposomes, and liposome-based drugs on the market and in clinical trials. Keywords: liposomes, nanomedicine, drug delivery, ultrastructur

    Biomimetic implant surface functionalization with liquid L-PRF products: in vitro study

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    Abstract Objective: Platelet-rich fibrin (PRF) clots and membranes are autologous blood concentrates widely used in oral surgical procedures; less is known, however, about the liquid formulations of such products. The aim of this in vitro study is to assess the behavior of different implant surfaces when in contact with two liquid leucocyte- and platelet-rich fibrin (L-PRF) products. Methods: Six commercial pure titanium discs, of 9.5 mm diameter and 1.5 mm thickness, were used. Three of these samples had a micro/nano-rough surface; three were machined. Three different protocols were tested. Protocols involved the immersion of the samples in (1) a platelets, lymphocytes, and fibrinogen liquid concentrate (PLyF) for 10 minutes, (2) an exudate obtained from L-PRF clots rich in fibronectin and vitronectin for 5 minutes, and (3) the fibronectin/vitronectin exudate for 2 minutes followed by immersion in the PLyF concentrate for further 8 minutes. After these treatments, the samples were fixed and observed using a scanning electron microscope (SEM). Results: Under microscopic observation, (1) the samples treated with the PLyF concentrate revealed a dense fibrin network in direct contact with the implant surface and a significant number of formed elements of blood; (2) in the samples treated with the fibronectin/vitronectin exudates, only a small number of white and red blood cells were detectable; and (3) in samples exposed to the combined treatment, there was an apparent increase in the thickness of the fibrin layer. When compared to the machined surface, the micro/nano-rough samples showed an overall increased retention of fibrin, leading to a thicker coating. Conclusions: Liquid L-PRF products promote the formation of a dense fibrin clot on micro/nano-rough implant surfaces in vitro. The adjunctive treatment of surfaces with the fibronectin/vitronectin exudate could provide support to contact of the fibrin with the surface, though it is not essential for the clot formation. Further studies are necessary to better elucidate the properties and benefits of liquid L-PRF products

    Synthesis, characterization and biological evaluation of new promising copper complexes on different glioblastoma cell lines

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    Metal complexes, thanks to their biological and chemical diversities, have been the subject of growing interest for years as pharmaceutical agents in cancer diagnostics and therapy. Cisplatin is the most famous metal complex used in cancer therapy. Unfortunately, its use is limited by dose-dependent toxicity and by the onset of drug-resistance phenomena. In this frame, there is urgent need to develop new metal-drugs that act with different mechanisms of action. Anticancer copper-compounds are excellent candidates to substitute platinum-base chemotherapeutics on the basis of the hypothesis that endogenous metals may be less toxic. Copper is involved in many biological pathways and it is an essential element for cellular growth and development. In particular, copper is involved in three typical tumoral pathways: cell proliferation, stimulation of angiogenesis and metastasis. In addition, the concentration of copper in many cancerous tissues is higher than that of normal tissues. In this work, for the preparation of Cu(I) and Cu(II) complexes, the ligand LAd conjugated with the biomolecule 1-adamantylamine has been used. In particular, for the synthesis of Cu(I) complexes the coligands triphenylphosphine (PPh3) and 1,3,5-Triaza-7-phosphaadamantane (PTA) have been employed. For Cu(II) complexes the acceptors copper(II) chlorine and copper(II) bromine have been selected. The antitumoral activity of the new Cu(I) and Cu(II) complexes has been evaluated on U87 and LN18 glioblastoma cell lines by MTT assay. Preliminary results showed that the most promising compounds able to inhibit cancer cell proliferation are those bearing the PPh3 moiety. In order to clarify the mechanisms of cancer cell death induced by the synthetized copper complexes, imaging analyses will be carried out by fluorescence and scanning electron microscopy as well as functional studies (proliferation, cell cycle, cell death marker expression) by flow cytometry

    Interferon-ε as potential inhibitor of Chlamydia trachomatis infection

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    Chlamydia trachomatis, the main cause of bacterial sexually transmitted diseases, is responsible for severe reproductive sequelae. Amongst all the cytokines involved in host immunity towards this pathogen, IFN-ε has recently acquired importance for its potential contribution to the female reproductive tract innate defenses. Herein, our study aimed to explore, for the first time, the activity of IFN-ε toward C. trachomatis in an in vitro infection model, by testing its effects on the different phases of chlamydial developmental cycle, as well as on the ultrastructural characteristics of chlamydial inclusions, via transmission electron microscopy. Main result is the capability of IFN-ε to alter C. trachomatis growth, as suggested by reduced infectious progenies, as well as a patchy distribution of bacteria and altered morphology of reticulate bodies within inclusions. In conclusion, our results suggest that IFN-ε could play a role in the innate and adaptive immune defenses against C. trachomatis; in the future, it will be needed to investigate its activity on an infection model more closely resembling the physiological environment of the female genital tract

    Effect of preparation protocol on physicochemical features and biointeractions of pegylated liposomes

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    Poly(ethylene glycol) (PEG) stabilized liposomes are widely used in drug delivery research because these surface grafted polymers stabilize liposomes in blood stream. However, hydrophilic polymers also affect lipid membrane organization and it is fundamental to investigate their effect on the physicochemical properties of lipid bilayers as well as on their interaction with biological membrane. PEG monolaurate was included in liposomes formulated with dimyristoyl-sn-glycero-3-phosphocholine and one of two cationic gemini surfactants that differ each other for the configuration of a stereogenic center on the polar headgroup. These formulations previously showed good efficiency as drug and DNA delivery systems. The effect of the presence of different amounts of a PEG-lipid and of the liposome preparation protocol was investigated by turbidimetry, dynamic laser light scattering, differential scanning calorimetry and electrophoretic mobility. Flow cytometry and laser scanning confocal microscopy on murine (C6) and on human glioblastoma (LN229) cell lines were also carried out to evaluate the influence of pegylation and of the protocol of preparation on the interaction of liposomes with the biological milieu
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